We propose to study how substrates bind to enzymes during catalysis using Resonance Raman Spectroscopy. Resonance Raman Spectroscopy can yield detailed information concerning the molecular properties of in situ substrates unavailable by other methods. We have recently obtained Raman spectrum of reduced nicotinamide adenine dinucleotide (NADH) when bound to liver alcohol dehydrogenase (LADH). NADH is the coenzyme to pyridine-linked dehydrogenase, a major class of enzymes involved in all areas of metabolism. Marked changes in the Raman spectrum of NADH occur when it forms the binary LADH/NADH complex. We intend to obtain and understand the Raman spectra of NADH and NAD+ (the oxidized form of NADH) when bound to the active sites of selected dehydrogenases. We also intend to study the changes in the Raman spectrum of the aldehyde substrates of LADH upon binding. We have selected two such substrates: retinal, a relatively good substrate of LADH, and DABA, a relatively poor one. These studies can greatly enhance our understanding of how enzymes function on a molecular level. We also propose to develop a coherent theoretical program to interpret our data in detailed molecular terms.